Acute kidney injury (AKI) is a serious and common complication of major surgery. This narrative review focuses on the relationship between perioperative red blood cell transfusion and AKI after cardiac surgery with cardiopulmonary bypass (CPB). Numerous observational studies have shown that these two factors are independently associated with each other. Several lines of evidence suggest that the nature of this association is one of cause and effect. The pathophysiological mechanism by which transfusions might harm the kidney has not been fully elucidated, but it is known that erythrocytes undergo irreversible morphological and biochemical changes during storage. As a result, after transfusion, they can promote a pro-inflammatory state, impair tissue oxygen delivery, and exacerbate tissue oxidative stress. This in turn can cause AKI in susceptible patients undergoing cardiac surgery with CPB, such as those with pre-existing kidney dysfunction or anaemia. Interventions aimed at avoiding perioperative blood transfusion might, therefore, reduce the risk of AKI after cardiac and other types of surgery.